tbuckley/cabot-search huggingface dataset:
Improved seizure control in patients with recurrent glioblastoma treated with bevacizumab
Authors: Caroline Hertler, Katharina Seystahl, Emilie Le Rhun, Hans-Georg Wirsching, Patrick Roth, Michael Weller, Dorothee Gramatzki
Journal: Neuro-Oncology (2022)

Journal Article Improved seizure control in patients with recurrent glioblastoma treated with bevacizumab Get access Caroline Hertler, Caroline Hertler Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, SwitzerlandCompetence Center for Palliative Care, University Hospital Zurich, Zurich, Switzerland https://orcid.org/0000-0001-6181-2895 Search for other works by this author on: Oxford Academic PubMed Google Scholar Katharina Seystahl, Katharina Seystahl Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Emilie Le Rhun, Emilie Le Rhun Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, SwitzerlandDepartment of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans-Georg Wirsching, Hans-Georg Wirsching Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrick Roth, Patrick Roth Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Weller, Michael Weller Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland https://orcid.org/0000-0002-1748-174X Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothee Gramatzki Dorothee Gramatzki Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland Corresponding Author: Dorothee Gramatzki, MD, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland (dorothee.gramatzki@usz.ch). https://orcid.org/0000-0002-9054-5498 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 11, November 2022, Pages 2001–2004, https://doi.org/10.1093/neuonc/noac172 Published: 30 July 2022 Article history Corrected and typeset: 30 July 2022 Published: 30 July 2022
Gut Microbiome in Colorectal Cancer: Clinical Diagnosis and Treatment
Authors: Yali Liu, Harry Cheuk-Hay Lau, Wing Yin Cheng, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Colorectal cancer (CRC) is one of the most frequently diagnosed cancers and the leading cause of cancer-associated deaths. Epidemiological studies have shown that both genetic and environmental risk factors contribute to the development of CRC. Several metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal malignancy. Although enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC, the precise mechanisms involved remain elusive. Recent data have shown a direct causative role of the gut microbiome in DNA damage, inflammation, and drug resistance in CRC, suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and therapy. Here, we provide an overview of the relationship between gut microbiome and CRC, and explore relevant mechanisms of colorectal tumorigenesis. We next highlight the potential of bacterial species as clinical biomarkers, as well as their roles in therapeutic response. Factors limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.
Karyotype engineering reveals spatio-temporal control of replication firing and gene contacts
Authors: Luciana Lazar-Stefanita, Jingchuan Luo, Remi Montagne, Agnes Thierry, Xiaoji Sun, Guillaume Mercy, Julien Mozziconacci, Romain Koszul, Jef D. Boeke
Journal: Cell Genomics (2022)

Eukaryotic genomes vary in terms of size, chromosome number, and genetic complexity. Their temporal organization is complex, reflecting coordination between DNA folding and function. Here, we used fused karyotypes of budding yeast to characterize the effects of chromosome length on nuclear architecture. We found that size-matched megachromosomes expand to occupy a larger fraction of the enlarged nucleus. Hi-C maps reveal changes in the three-dimensional structure corresponding to inactivated centromeres and telomeres. De-clustering of inactive centromeres results in their loss of early replication, highlighting a functional correlation between genome organization and replication timing. Repositioning of former telomere-proximal regions on chromosome arms exposed a subset of contacts between flocculin genes. Chromatin reorganization of megachromosomes during cell division remained unperturbed, and it revealed that centromere-rDNA contacts in anaphase, extending over 0.3 Mb on wild-type chromosome, cannot exceed ∼1.7 Mb. Our results highlight the relevance of engineered karyotypes to unveiling relationships between genome organization and function.
Childhood immunization services accessibility and utilization during the COVID-19 pandemic in Africa
Authors: Tafadzwa Dzinamarira, Enos Moyo, Perseverance Moyo, Gashema Pierre, Etienne Mpabuka, Morris Kahere, Nigel Tungwarara, Itai Chitungo, Grant Murewanhema, Godfrey Musuka
Journal: Journal of Infection (2022)
Review of the British Thoracic Society Winter Meeting 2021, 24–26 November 2021
Authors: Akhilesh Jha, Tom Ward, Steven Walker, Amanda T Goodwin, James D Chalmers
Journal: Thorax (2022)

The Winter Meeting of the British Thoracic Society (BTS) is a platform for the latest clinical and scientific research in respiratory medicine. This review summarises the key symposia and presentations from the BTS Winter Meeting 2021 held online due to the COVID-19 pandemic.
Young woman with multiple lung nodules: a pulmonary oxymoron
Authors: Hiromu Tanaka, Hiroki Kabata, Katsura Emoto, Shigenori Hayashi, Kyohei Masai, Koichi Fukunaga
Journal: Thorax (2022)

<h3>Introduction</h3> Idiopathic REM sleep behaviour(iRBD) disorder represents the most specific prodromal marker of an impending synucleinopathy with over 90% developing either Parkinson's disease(PD), Dementia with Lewy Bodies(DLB) or Multiple System Atrophy(MSA) after 15 years. This finding has stimulated efforts to actively register and track progression of such patients. Here we present experience of a biobanking program established with the aim of identifying prodromal synucleinopathies to facilitate recruitment to neuroprotective trials as they become available. <h3>Methods</h3> Patients with iRBD were prospectively and sequentially recruited. Cross-sectional comparator groups consisting of healthy controls, idiopathic PD (within 5 years of diagnosis) and DLB were also recruited. Patients underwent a standardized assessment protocol including clinical phenotyping, neuropsychometric testing, multimodal MRI, polysomnography, quantitative electroencephalography, chronobiology (melatonin and clock gene expression profiling) and gait testing. Subjects were invited for annual and biennial review. <h3>Results</h3> 102 patients have been recruited into the study since July 2016 including 35 patients with iRBD, 26 DLB, 19 early PD and 16 controls. 15 patients have returned for follow-up with 3 converting to a synucleinopathy(2 DLB, 1 PD). 75% of participants were able to complete all elements of assessment protocol. Preliminary evaluation of iRBD participants reveals early changes in clock gene expression(BMAL1) and subtle changes in patterns of gait compared to older controls. <h3>Conclusions</h3> Our preliminary findings demonstrate utility and feasibility of a prodromal biobanking program within the Australian context aimed at identifying prodromal synucleinopathies. Similar models can be applied to other centers to improve access and create an extended national collaborative network.
Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis
Authors: Brigida Barberio, David J Gracie, Christopher J Black, Alexander C Ford
Journal: Gut (2022)

There are numerous biological therapies and small molecules licensed for luminal Crohn's disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.
Preterm or early term birth and long-term risk of asthma into midadulthood: a national cohort and cosibling study
Authors: Casey Crump, Jan Sundquist, Kristina Sundquist
Journal: Thorax (2022)

Background Preterm birth is associated with pulmonary complications early in life; however, long-term risks of asthma into adulthood are unclear. Objective To determine asthma risks from childhood into adulthood associated with gestational age at birth in a large population-based cohort. Methods A national cohort study was conducted of all 4 079 878 singletons born in Sweden during 1973–2013, followed up for asthma identified from primary care, specialty outpatient and inpatient diagnoses in nationwide registries through 2018 (up to 46 years). Cox regression was used to adjust for potential confounders, and cosibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors. Results In 91.9 million person-years of follow-up, 607 760 (14.9%) persons were diagnosed with asthma. Preterm birth was associated with increased risk of asthma at ages &lt;10 years (adjusted HR 1.73; 95% CI 1.70 to 1.75), 10–17 years (1.29; 1.27 to 1.32) and 18–46 years (1.19; 1.17 to 1.22). Across all ages, adjusted HRs further stratified were 3.01 (95% CI 2.88 to 3.15) for extremely preterm (22–27 weeks), 1.76 (1.72 to 1.79) for very or moderately preterm (28–33 weeks), 1.31 (1.29 to 1.32) for late preterm (34–36 weeks) and 1.13 (1.12 to 1.14) for early term (37–38 weeks), compared with full-term (39–41 weeks) birth. These findings were not explained by shared familial factors. Asthma risks were elevated after spontaneous or medically indicated preterm birth and with or without perinatal respiratory complications. Conclusions In this large national cohort, preterm and early term birth were associated with increased risks of asthma from childhood into midadulthood. Persons born prematurely need long-term follow-up into adulthood for timely detection and treatment of asthma.
Is the Mutation Rate Lower in Genomic Regions of Stronger Selective Constraints?
Authors: Haoxuan Liu, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2022)

Abstract A study of the plant Arabidopsis thaliana detected lower mutation rates in genomic regions where mutations are more likely to be deleterious, challenging the principle that mutagenesis is blind to its consequence. To examine the generality of this finding, we analyze large mutational data from baker's yeast and humans. The yeast data do not exhibit this trend, whereas the human data show an opposite trend that disappears upon the control of potential confounders. We find that the Arabidopsis study identified substantially more mutations than reported in the original data-generating studies and expected from Arabidopsis' mutation rate. These extra mutations are enriched in polynucleotide tracts and have relatively low sequencing qualities so are likely sequencing errors. Furthermore, the polynucleotide “mutations” can produce the purported mutational trend in Arabidopsis. Together, our results do not support lower mutagenesis of genomic regions of stronger selective constraints in the plant, fungal, and animal models examined.
Nasopharyngeal lipidomic endotypes of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study
Authors: Michimasa Fujiogi, Zhaozhong Zhu, Yoshihiko Raita, Tadao Ooka, Juan C Celedon, Robert Freishtat, Carlos A Camargo, Kohei Hasegawa
Journal: Thorax (2022)

Bronchiolitis is the leading cause of hospitalisation of US infants and an important risk factor for childhood asthma. Recent evidence suggests that bronchiolitis is clinically heterogeneous. We sought to derive bronchiolitis endotypes by integrating clinical, virus and lipidomics data and to examine their relationship with subsequent asthma risk.
Bayesian Phylogenetic Inference using Relaxed-clocks and the Multispecies Coalescent
Authors: Tomáš Flouri, Jun Huang, Xiyun Jiao, Paschalia Kapli, Bruce Rannala, Ziheng Yang
Journal: Molecular Biology and Evolution (2022)

Abstract The multispecies coalescent (MSC) model accommodates both species divergences and within-species coalescent and provides a natural framework for phylogenetic analysis of genomic data when the gene trees vary across the genome. The MSC model implemented in the program bpp assumes a molecular clock and the Jukes–Cantor model, and is suitable for analyzing genomic data from closely related species. Here we extend our implementation to more general substitution models and relaxed clocks to allow the rate to vary among species. The MSC-with-relaxed-clock model allows the estimation of species divergence times and ancestral population sizes using genomic sequences sampled from contemporary species when the strict clock assumption is violated, and provides a simulation framework for evaluating species tree estimation methods. We conducted simulations and analyzed two real datasets to evaluate the utility of the new models. We confirm that the clock-JC model is adequate for inference of shallow trees with closely related species, but it is important to account for clock violation for distant species. Our simulation suggests that there is valuable phylogenetic information in the gene-tree branch lengths even if the molecular clock assumption is seriously violated, and the relaxed-clock models implemented in bpp are able to extract such information. Our Markov chain Monte Carlo algorithms suffer from mixing problems when used for species tree estimation under the relaxed clock and we discuss possible improvements. We conclude that the new models are currently most effective for estimating population parameters such as species divergence times when the species tree is fixed.
Serum proteomic profiling of rheumatoid arthritis–interstitial lung disease with a comparison to idiopathic pulmonary fibrosis
Authors: Xiaoping Wu, Yunju Jeong, Sergio Poli de Frías, Imaani Easthausen, Katherine Hoffman, Clara Oromendia, Shahrad Taheri, Anthony J Esposito, Luisa Quesada Arias, Ehab A Ayaub, Rie Maurer, Ritu R Gill, Hiroto Hatabu, Mizuki Nishino, Michelle L Frits, Christine K Iannaccone, Michael E Weinblatt, Nancy A Shadick, Paul F Dellaripa, Augustine M K Choi, Edy Y Kim, Ivan O Rosas, Fernando J Martinez, Tracy J Doyle
Journal: Thorax (2022)

Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets.
Genome Sequencing of up to 6,000-Year-Old<i>Citrullus</i>Seeds Reveals Use of a Bitter-Fleshed Species Prior to Watermelon Domestication
Authors: Oscar A Pérez-Escobar, Sergio Tusso, Natalia A S Przelomska, Shan Wu, Philippa Ryan, Mark Nesbitt, Martina V Silber, Michaela Preick, Zhangjun Fei, Michael Hofreiter, Guillaume Chomicki, Susanne S Renner
Journal: Molecular Biology and Evolution (2022)

Iconographic evidence from Egypt suggests that watermelon pulp was consumed there as a dessert by 4,360 BP. Earlier archaeobotanical evidence comes from seeds from Neolithic settlements in Libya, but whether these were watermelons with sweet pulp or other forms is unknown. We generated genome sequences from 6,000- and 3,300-year-old seeds from Libya and Sudan, and from worldwide herbarium collections made between 1824 and 2019, and analyzed these data together with resequenced genomes from important germplasm collections for a total of 131 accessions. Phylogenomic and population-genomic analyses reveal that (1) much of the nuclear genome of both ancient seeds is traceable to West African seed-use "egusi-type" watermelon (Citrullus mucosospermus) rather than domesticated pulp-use watermelon (Citrullus lanatus ssp. vulgaris); (2) the 6,000-year-old watermelon likely had bitter pulp and greenish-white flesh as today found in C. mucosospermus, given alleles in the bitterness regulators ClBT and in the red color marker LYCB; and (3) both ancient genomes showed admixture from C. mucosospermus, C. lanatus ssp. cordophanus, C. lanatus ssp. vulgaris, and even South African Citrullus amarus, and evident introgression between the Libyan seed (UMB-6) and populations of C. lanatus. An unexpected new insight is that Citrullus appears to have initially been collected or cultivated for its seeds, not its flesh, consistent with seed damage patterns induced by human teeth in the oldest Libyan material.
A lncRNA fine-tunes salicylic acid biosynthesis to balance plant immunity and growth
Authors: Ningkun Liu, Yanzhuo Xu, Qi Li, Yuxin Cao, Dechang Yang, Shasha Liu, Xiaokang Wang, Yingjie Mi, Yang Liu, Chenxi Ding, Yan Liu, Yong Li, Yao-Wu Yuan, Ge Gao, Jinfeng Chen, Weiqiang Qian, Xiaoming Zhang
Journal: Cell Host & Microbe (2022)

Constitutive activation of plant immunity is detrimental to plant growth and development. Here, we uncover the role of a long non-coding RNA (lncRNA) in fine-tuning the balance of plant immunity and growth. We find that a lncRNA termed salicylic acid biogenesis controller 1 (SABC1) suppresses immunity and promotes growth in healthy plants. SABC1 recruits the polycomb repressive complex 2 to its neighboring gene NAC3, which encodes a NAC transcription factor, to decrease NAC3 transcription via H3K27me3. NAC3 activates the transcription of isochorismate synthase 1 (ICS1), a key enzyme catalyzing salicylic acid (SA) biosynthesis. SABC1 thus represses SA production and plant immunity via decreasing NAC3 and ICS1 transcriptions. Upon pathogen infection, SABC1 is downregulated to derepress plant resistance to bacteria and viruses. Together, our findings reveal lncRNA SABC1 as a molecular switch in balancing plant defense and growth by modulating SA biosynthesis.
Hydrogel platform with tunable stiffness based on magnetic nanoparticles cross-linked GelMA for cartilage regeneration and its intrinsic biomechanism
Authors: Chenchen Zhou, Chunli Wang, Kang Xu, Zhixing Niu, Shujuan Zou, Demao Zhang, Zhiyong Qian, Jinfeng Liao, Jing Xie
Journal: Bioactive Materials (2022)

Cartilage injury affects numerous individuals, but the efficient repair of damaged cartilage is still a problem in clinic. Hydrogel is a potent scaffold candidate for tissue regeneration, but it remains a big challenge to improve its mechanical property and figure out the interaction of chondrocytes and stiffness. Herein, a novel hybrid hydrogel with tunable stiffness was fabricated based on methacrylated gelatin (GelMA) and iron oxide nanoparticles (Fe2O3) through chemical bonding. The stiffness of Fe2O3/GelMA hybrid hydrogel was controlled by adjusting the concentration of magnetic nanoparticles. The hydrogel platform with tunable stiffness modulated its cellular properties including cell morphology, microfilaments and Young's modulus of chondrocytes. Interestingly, Fe2O3/GelMA hybrid hydrogel promoted oxidative phosphorylation of mitochondria and facilitated catabolism of lipids in chondrocytes. As a result, more ATP and metabolic materials generated for cellular physiological activities and organelle component replacements in hybrid hydrogel group compared to pure GelMA hydrogel. Furthermore, implantation of Fe2O3/GelMA hybrid hydrogel in the cartilage defect rat model verified its remodeling potential. This study provides a deep understanding of the bio-mechanism of Fe2O3/GelMA hybrid hydrogel interaction with chondrocytes and indicates the hydrogel platform for further application in tissue engineering.
Glucagon-like Peptide-1 Receptor-based Therapeutics for Metabolic Liver Disease
Authors: Julian M Yabut, Daniel J Drucker
Journal: Endocrine Reviews (2022)

Abstract Glucagon-like peptide-1 (GLP-1) controls islet hormone secretion, gut motility, and body weight, supporting development of GLP-1 receptor agonists (GLP-1RA) for the treatment of type 2 diabetes (T2D) and obesity. GLP-1RA exhibit a favorable safety profile and reduce the incidence of major adverse cardiovascular events in people with T2D. Considerable preclinical data, supported by the results of clinical trials, link therapy with GLP-RA to reduction of hepatic inflammation, steatosis, and fibrosis. Mechanistically, the actions of GLP-1 on the liver are primarily indirect, as hepatocytes, Kupffer cells, and stellate cells do not express the canonical GLP-1R. GLP-1RA reduce appetite and body weight, decrease postprandial lipoprotein secretion, and attenuate systemic and tissue inflammation, actions that may contribute to attenuation of metabolic-associated fatty liver disease (MAFLD). Here we discuss evolving concepts of GLP-1 action that improve liver health and highlight evidence that links sustained GLP-1R activation in distinct cell types to control of hepatic glucose and lipid metabolism, and reduction of experimental and clinical nonalcoholic steatohepatitis (NASH). The therapeutic potential of GLP-1RA alone, or in combination with peptide agonists, or new small molecule therapeutics is discussed in the context of potential efficacy and safety. Ongoing trials in people with obesity will further clarify the safety of GLP-1RA, and pivotal studies underway in people with NASH will define whether GLP-1–based medicines represent effective and safe therapies for people with MAFLD.
Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance
Authors: Komal Agrawal, Li Ching Ong, Susan Monkley, Kristofer Thörn, Elisabeth Israelsson, Engin Baturcam, Cassie Rist, Karin Schön, Sophia Blake, Björn Magnusson, James Cartwright, Suman Mitra, Abilash Ravi, Nazanin Zounemat-Kermani, Jayendra Kumar Krishnaswamy, Nils Y. Lycke, Ulf Gehrmann, Johan Mattsson
Journal: Journal of Allergy and Clinical Immunology (2022)